Iranian Journal of Pediatric Hematology and Oncology
Volume:11 Issue: 4, Autumn 2021

Epigenetic regulation such as DNA methylation plays a major role in chromatin organization and gene transcription. Additionally, histone modification is an epigenetic regulator of chromatin structure and influences chromatin organization and gene expression. The relationship between DNA methyltransferase (DNMTs) expression and promoter methylation of the tumor suppressor genes (TSGs) has been reported in various cancers. Previously, the effect of 5-aza-2chr('39')-deoxycytidine (5-AZA-CdR), trichostatin A (TSA), and valproic acid (VPA) was shown on various cancers. This study aimed to investigate the effect of 5chr('39')-fluoro-2chr('39')-deoxycytidine (FdCyd) and sodium butyrate on the genes of the intrinsic apoptotic pathway, p21, p53, cell viability, and apoptosis in human hepatocellular carcinoma SNU449, SNU475, and SNU368 cell lines.

In this lab trial study, the SNU449, SNU475, and SNU368 cells were cultured and treated with 5chr('39')-fluoro-2chr('39')-deoxycytidine and sodium butyrate. To determine cell viability, cell apoptosis, and the relative gene expression level, MTT assay, flow cytometry assay, and qRT-PCR were done respectively.

5chr('39')-fluoro-2chr('39')-deoxycytidine and sodium butyrate changed the expression level of the BAX, BAK, APAF1, Bcl-2, Bcl-xL, p21, and p53 gene (P<0.0001) by which induced cell apoptosis and inhibit cell growth in all three cell lines, SNU449, SNU475, and SNU368. 

Both compounds played their roles through the intrinsic apoptotic pathway to induce cell apoptosis.

Cardiomyopathy usually causes a cardiac dysfunction resistant to treatment due to anthracycline. This study aimed to evaluate the changes in Tei-Index (myocardial performance index) in patients with malignancies treated with anthracycline.

This case-control study was done on 15 children who were treated with low-dose anthracycline (1-199mg/kg) called group A and 15 children who were treated with high dose (>200mg/kg) anthracycline called group B after acquiring consent from their parents. Children with no abnormality in Echo-Doppler results were included in this study. The patients’ age range between 1- 17 years with a mean age of 6.57 years. Another group of healthy children were assigned to group C as a control group who had not received chemotherapy. The first echo was performed right before the treatment and the second one, two weeks after completing chemotherapy.  Data were analyzed by the SPSS statistical software.

Changes in mean Tei-index in group A were 0.36 ± 0.04 before treatment and 0.43 ± 0.11 after treatment. Changes in mean Tei-index in group B were 0.37 ± 0.04 before treatment and 0.45 ± 0.06 after treatment. There was no significant difference between the two groups using the independent T-test. (p-value= 0.57). No significant correlation between the changes in mean ejection fraction (EF) and treatment was found in the three groups (p-value=0.45).

This study showed a change in the Tei-index (MPI) in patients receiving anthracycline; regardless of the dosage, they got in their regimen. Given the use of anthracycline, any abnormal cardiac finding can alert the physicians to the possibility of cardiomyopathy, hence scheduling routine follow-ups are necessary.

Leukemia accounts for about 8% of all cancers and causes approximately 7% of mortalities due to malignancies. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and rare in older subjects. The aim of this study was to evaluate the expression of oxidative stress resistance genes including Catalase, manganese superoxide dismutase (MnSOD), Forkhead Box O3 (Foxo3a), and sirtuin-1 (SIRT1) in ALL patients that may be applied for therapeutic purposes in the future.

In this observational case-control study, blood samples were drawn from 60 newly diagnosed ALL patients and 10 healthy individuals as a control group. After RNA extraction and cDNA synthesis, real-time polymerase chain reaction (RT-PCR) amplification was performed using specific primers for evaluating the expression of Catalase, MnSOD, Foxo3a, and SIRT1 genes.

The expression of all studied genes were significantly higher in ALL patients than in the control group; catalase gene, FOX gene, MnSOD gene, and SIRT1 gene were expressed 4 times (p =0.04), 4.5 times (p =0.001), 2.2 times (p =0.05) and 4.8 (p =0.01) times higher than healthy individuals in the control group respectively. However, no significant relationship between their expression and the stage of the disease and blast percentage was demonstrated (P>0.05).

According to these results, the authors believe that the pathways involved in oxidative stress may be one of the most important causes of ALL diseasechr('39')s development and progression. In this regard, targeting the critical genes of these pathways can be considered a potential treatment with fewer side effects.

In pediatric care settings, intravenous cannulation (IVC) is usually needed for diverse purposes. Considering the painfulness and invasiveness of sampling by direct venipuncture (DVP), using a painless and less invasive method would be promising. Therefore, this study aimed to compare the effect of substitution of routine DVP with direct blood sampling through IVC on the accuracy of hematologic results.

This was a cross-sectional study conducted on 5-14-year-old children admitted to the emergency ward of 17th Shahrivar Pediatric Hospital in Rasht, north of Iran. After discarding only one ml of blood, paired-samples were taken from IVC and DVP and analyzed for 30 most frequently requested electrolytes, hematologic, and blood gas tests. The similarity of the obtained results by the two methods indicated the probability of substituting DVP with IVC and was defined by the absence of significant statistical difference (P>0.05).

The comparison between the mean of hematologic factors by two methods showed significant similarity between groups regarding all parameters (P>0.05) except the mean of red blood cell count in the two groups (P<0.05). Assessing the level of electrolytes by two collection methods showed that there was a significant similarity between the mean of all parameters (P>0.05) except for phosphorus (P=.002). Furthermore, assessing the level of electrolytes showed a significant similarity between the potential of hydrogen, partial pressure of carbon dioxide, bicarbonate, and buffer base in the two groups (P>0.05). However, there was a significant difference between partial pressure of oxygen, base excess, and O2 saturation in the two collection methods (P<0.05).

Based on the promising results obtained in this study, it seems that these methods could be interchangeably used, and IVC can be an alternative method for DVP by discarding the minimum amount of blood and less invasiveness in children.

Frequent blood transfusion can lead to iron overload which is potentially dangerous for the heart and liver. Silymarin has well-documented protective effects on hepatocytes. The purpose of this study was to evaluate the hepatoprotective effects of silymarin addition to iron chelators in children with thalassemia.

This randomized, double-blinded, and placebo-controlled trial was performed on 40 subjects with thalassemia major and intermedia in Amir Kabir Hospital, Arak, Iran. Subjects were randomized 1:1 oral to 30 mg/kg deferasirox plus placebo, or deferasirox plus oral 70-140 mg silymarin (twice daily) for 6 months. Cardiac and hepatic iron levels and levels of Gamma-glutamyltransferase (GGT), Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, albumin, total protein, and total cholesterol were measured at baseline and after 6 months of treatment.

The mean age of patients was 16 years and 60% of patients were female. After 6 months, there were significant increases in the levels of ALT, AST, GGT, and TG in the placebo group as compared to the silymarin group (P < 0.05). In contrast, ALT, AST, and GGT had significant reductions compared to the silymarin group (P =0.05). Patients in the placebo group had a rise in total bilirubin (P = 0.07), but total protein and albumin did not have significant changes in the silymarin group (P > 0.05). Finally, a significant improvement was noted in cardiac iron values in patients using silymarin; 22.2 ± 6.6 ms at baseline vs 26.9 ± 7.1 ms at 6 months (P < 0.05).

This study suggests that twice-daily addition of silymarin to deferasirox could improve liver function in children with thalassemia major and intermedia. Silymarin seems safe in pediatrics.

The aim of this study was to compare the epochs before and after the revision of the transfusion guideline, and determine their effects on transfusion rates and short-term outcomes in preterm infants.

This retrospective study was conducted to investigate the effect of the new transfusion guideline. Infants who were born <32 weeks of gestation and received red blood cell (RBC) transfusion in their first 6-weeks of life were divided into two epochs according to adopting the new transfusion guideline. The demographic and clinical data of the patients were compared between these two periods.

Fifty-six infants were included (Period 1, n=22; Period, n=34). The number of transfusions, total and cumulative volume of the transfusions were similar in the two periods. There was an inverse relationship between the gestational age and the number of transfusions in both periods (r=-0.575, p=0.005, and r=-0.494, p=0.003), and there was an inverse relationship between the birth weight and the number of transfusions in period 2 (r=-0.423, p=0.013). The ratio of total phlebotomy volume to estimated total blood volume was higher in period 2 (p=0.029). There was a direct relationship between the phlebotomy loss and volume of RBC transfused in period 2 (r=0.487, p=0.003). The incidence of morbidities was similar in the two periods.

Changing only the transfusion protocol did not decrease the transfusion number. Although transfusion guidelines were adopted rigorously, it seems to be impossible to reduce RBC transfusion rates unless anemia prevention strategies were also in place.

Global cancer statistics will continue to grow in the coming years. Leukemia is the fifth leading cause of death in the world and the second one in Iran; therefore, it is very important to study the affected areas, including the cardiovascular system in this disease. In heart cancer, tumors whose primary origin is the heart are called primary tumors, which are very rare. Tumors that originate in other parts of the body and spread to the heart are called secondary tumors. Although heart cancer is still rare, most cancers found in the heart come from other parts of the body and are considered as secondary tumors. The symptoms of metastatic heart cancer vary and depend on the location and extent of the lesion. Cancer can also affect the heart in other ways. One of these ways is the effect of the treatments used, which is reported among acute lymphocytic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia due to the use of tyrosine kinase inhibitors as the main drug in reducing mortality among these patients. Pericardial involvement is reported to be the most common cardiovascular complication of drug use among different kinds of leukemias. In this article, we try to collect cardiovascular evidence related to acute lymphocytic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia, separately.

Methemoglobinemia is a rare autosomal recessive genetic disease caused by disruptive mutations in the CYB5R3 gene (MIM: 250800). Herein, a novel mutation is reported in an Iranian patient affected with methemoglobinemia type II. In this case study, the patient is precisely described according to the thoroughly carried-out examinations and workups. In so doing, the peripheral blood sample was collected to evaluate the methemoglobin level and NADH-CYB5R3 activity test. Moreover, whole-exome sequencing (WES) was recruited to identify the mutation leading to this disorder. Subsequently, Sanger sequencing was employed to confirm the detected mutation. Magnetic Resonance Imaging was also performed to explore the structure of the brain. As identified by the blood test, the methemoglobin level increased up to 25%, and the NADH-CYB5R3 enzyme activity showed to be 13.8 IU/g of Hb. A novel homozygous mutation in CYB5R3 (NM_001171661: g.23435C>T, c.181C>T, p.R61X, rs1210302322) was identified as the cause of the Methemoglobinemia type II in the proband. This nonsense mutation alters arginine to the stop codon at position 61 of protein in the FAD-binding domain that results in a truncated protein. The MRI revealed brain atrophy and corpus calusom hypoplasticity. It was established that this variation can lead to Methemoglobinemia. The proband demonstrates Methemoglobinemia type II phenotype such as cyanosis, severe mental retardation, microcephaly, as well as developmental delay. The brain MRI revealed brain atrophy and corpus calusom hypoplasticity.The cyanosis symptom is managed by daily ascorbic acid uptake.